Array assays between surface bound binding agents or probes and target molecules in solution may be used to detect the presence of particular biopolymeric analytes in the solution. The surface-bound probes may be oligonucleotides, peptides, polypeptides, proteins, antibodies or other molecules capable of binding with target biomolecules in the solution. Such binding interactions are the basis for many of the methods and devices used in a variety of different fields, e.g., genomics (in sequencing by hybridization, SNP detection, differential gene expression analysis, identification of novel genes, gene mapping, finger printing, etc.) and proteomics.
One typical array assay method involves biopolymeric probes immobilized in an array on a substrate such as a glass substrate or the like. A solution containing target molecules (“targets”) that bind with the attached probes is placed in contact with the bound probes under conditions sufficient to promote binding of targets in the solution to the complementary probes on the substrate to form a binding complex that is bound to the surface of the substrate. The pattern of binding by target molecules to probe features or spots on the substrate produces a pattern, i.e., a binding complex pattern, on the surface of the substrate which is detected. This detection of binding complexes provides desired information about the target biomolecules in the solution.
The binding complexes may be detected by reading or scanning the array with, for example, optical means, although other methods may also be used, as appropriate for the particular assay. For example, laser light may be used to excite fluorescent labels attached to the targets, generating a signal only in those spots on the array that have a labeled target molecule bound to a probe molecule. This pattern may then be digitally scanned for computer analysis. Such patterns can be used to generate data for biological assays such as the identification of drug targets, single-nucleotide polymorphism mapping, monitoring samples from patients to track their response to treatment, assessing the efficacy of new treatments, etc.
Biopolymer arrays can be fabricated using either deposition of the previously obtained biopolymers or in situ synthesis methods. The deposition methods basically involve depositing biopolymers at predetermined locations on a substrate which are suitably activated such that the biopolymers can link thereto. Biopolymers of different sequence may be deposited at difference regions on the substrate to yield the completed array. Typical procedures known in the art for deposition of previously obtained polynucleotides, particularly DNA, such as whole oligomers or cDNA, are to load a small volume of DNA in solution in one or more drop dispensers such as the tip of a pin or in an open capillary and, touch the pin or capillary to the surface of the substrate. Such a procedure is described in U.S. Pat. No. 5,807,522. When the fluid touches the surface, some of the fluid is transferred. The pin or capillary must be washed prior to picking up the next type of DNA for spotting onto the array. This process is repeated for many different sequences and, eventually, the desired array is formed. Alternatively, the DNA can be loaded into a drop dispenser in the form of a pulse jet head and fired onto the substrate. Such a technique has been described PCT publications WO 95/25116 and WO 98/41531, “Multiple Reservoir Ink Jet Device for the Fabrication of Biomolecular Arrays,” Ser. No. 09/150,507 filed Sep. 9, 1998; U.S. Patent application publications 2003/0112295 and 2003/0113730; and patents including U.S. Pat. Nos. 6,242,266 and 6,613,893—as well as the references cited in each noted item (all, incorporated herein by reference) and others.
The in situ synthesis methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, as well as WO 98/41531 and the references cited therein for synthesizing polynucleotides (specifically, DNA) using phosphoramidite or other chemistry. Additional patents describing in situ nucleic acid array synthesis protocols and devices include U.S. Pat. Nos. 6,451,998; 6,446,682; 6,440,669; 6,420,180; 6,372,483; and 6,323,043—the disclosures of which patents are herein incorporated by reference.
Such in situ synthesis methods can be basically regarded as iterating the sequence of depositing droplets of: (a) a protected monomer onto predetermined locations on a substrate to link with either a suitably activated substrate surface (or with previously deposited deprotected monomer); (b) deprotecting the deposited monomer so that it can react with a subsequently deposited protected monomer; and (c) depositing another protected monomer for linking. Different monomers may be deposited at different regions on the substrate during any one cycle so that the different regions of the completed array will carry the different biopolymer sequences as desired in the completed array. One or more intermediate further steps may be required in each iteration, such as oxidation and washing steps.
Known in-situ DNA or other bioploymer microarray writers built in the past have used one type of printhead from one vendor. Writer software to control the printhead(s) was produced on an altogether custom basis in view of the printhead chosen and overall system design. Yet, for various reasons one might want to explore the possibilities of using different types of printheads, potentially from different vendors. Such an approach may offer a choice between printhead vendors at any point in the design process of a printer system or during a printer systems lifecycle. It may facilitate substantial system upgrades or provide adaptability in the event of the loss of a supplier. Still further, it would be desirable to produce a more transparent or less specialized system of control than presently available. In which case, lesser reliance may be placed on any particular individual if the system can be easily understood by those other than the original implementer. Such flexibility, again, moderates risk. In addition, it may offer freedom from using certain (possibly protected) firmware provided by the printhead vendor. Also, a specific printhead may not allow printing in a given desired pattern, upon a given desired media, temperature ranges, firing speeds, nozzle spacing, drop size, chemistrie(s). Furthermore, know systems do not allow for mixing different models of printhead assemblies form a single or multiple vendor.
Current printhead models differ from each other in many ways. Among these ways are: the number of different fluids that can be fired, the spacing of the nozzles, the arrangement of the nozzles, etc. Accordingly, it is presently the case that to change-over printhead control accommodating one printhead to another model would require substantial changes to the basic algorithms of the software that controls the writer. As such, there exists a need for producing writer/printhead control software that is not so bound-up with the hardware design it is intended to control that its utility is unduly limited.